Atypical Femoral Fractures - Osteoporosis...Atypical femoral fractures (AFF) • low-trauma stress...
Transcript of Atypical Femoral Fractures - Osteoporosis...Atypical femoral fractures (AFF) • low-trauma stress...
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Atypical Femoral Fractures
Angela M. Cheung MD, PhD, FRCPC
Professor of Medicine,University Health Network, University of Toronto
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Disclosures
Honoraria for CME events or advisory board:
Amgen Eli Lilly Gilead
Grants to my institution (UHN) for research / educational activities:
Amgen Clementia Mereo
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Learning Objectives
Definition and radiographic characteristics Epidemiology Clinical Risk Factors Surgical and Medical Management Canadian AFF Registry
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DEFINITION AND RADIOGRAPHIC CHARACTERISTICS
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Atypical femoral fractures (AFF)
• low-trauma stress fractures
• in subtrochanteric or shaft region of the femur
• specific radiographic findings
• can be associated with bisphosphonate therapy
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Journal of Bone and Mineral Research, Vol. 25, No. 11, November 2010, pp 2267-2294
Journal of Bone and Mineral Research, Vol. 29, No. 1, January 2014, pp 1-23
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Femur Fractures
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64yoF Caucasian with bilateral incomplete AFFs Typical Femoral
Stress Fracture
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Incomplete AFFs: Plain RadiographsLucent line
+
Focal periosteal
reaction
on lateral cortex
Beaking
Lucent line
+
Focal periosteal
reaction
on lateral cortex
Beaking
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Complete AFFs: Plain radiographs
ASBMR AFF Task Force Report, JBMR 2010, 25 (11): 2267
Transverse
fracture line
Subtrochanteric
Transverse
fracture line
Mid-diaphyseal
Focal Periosteal Reaction
on Lateral cortex
Medial spike
Oblique extension
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AFF: ASBMR Case Definition 2013
Major features (4 out of 5 criteria): Below lesser trochanter, above supracondylar flare
1. Little or no trauma2. Transverse (or mostly transverse) or short oblique configuration3. Non-comminuted (or minimally comminuted)4. Complete fractures extend through both cortices and may have a medial spike;
Incomplete fractures involve only the lateral cortex5. Localized periosteal or endosteal reaction of the lateral cortex
Minor features (none required): Generalized increase in cortical thickness Delayed healing Prodromal symptoms such as dull aching pain in groin or thigh Bilateral fractures and symptoms
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AFF: Key Clinical Feature
ASBMR Task Force review
75% have prodromal pain These features are fundamentally different from
common osteoporotic femur fractures and strongly suggest a distinct pathogenesis
Ontario AFF Cohort (n~300)
~80% have prodromal symptoms: pain, ache, weakness, loss of function
Shane et al., ASBMR Task Force Report, J Bone Miner Res 2010
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Specific radiographic findings
Plain X-raysBone Scan
MRI DXAASBMR AFF Task Force Report, JBMR 2010, 25 (11): 2282
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Magnification of HD-IVA
Densitometer-based femurscans
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EPIDEMIOLOGY
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Orwoll E, McClung MR. West J Med. 143(2):239-42, 1985 Aug
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• “In the context of declining typical hip fractures among the US elderly, we observed small but significant increases in the incidence of subtrochanteric fragility fractures”
• “we estimated that for every 100 or so reduction in typical femoral neck or intertrochanteric fractures, there was an increase of one subtrochanteric fragility fracture.”
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JAMA, February 23, 2011—Vol 305 (8): 783 JBMR,
Incidence of Complete AFFs
~1/1000 py after 8 - 9.9 years
~1-2/1000 py after 6 - 7 years
Ontario CANADA DataKaiser Permanente
California Data
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Globe and Mail… Article by Carly Weeks…June 2012
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CLINICAL RISK FACTORS
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Clinical Risk Factors
Age Sex Race Genetics Medical Conditions Drugs Bone characteristics
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Age and Sex
Mostly women, very few men
Younger women
Ontario AFF Cohort (n~320): Mean age ~70 yearsRange= 19 to 90 years
Dell et al. JBMR 27 (12):2544-2550, Dec 2012
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Race and Genetics Asians (Ontario AFF cohort, Kaiser
Permanente, Singapore and Asian groups)
Hypophosphatasia OI
Sutton R et al. JBMR
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Nguyen et al, JBMR Plus 1, 2017
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Medical Conditions
Rheumatoid Arthritis Vitamin D deficiency Diabetes Breast Cancer Dementia
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Drugs
Long duration of BP therapy Multiple anti-resorptive medications Glucocorticoid use PPIs
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Incidence of AFFs increase with duration of BP therapy
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BP exposure is heterogenous
Ontario AFF Cohort (n~320): Mean ~10.6 yearsRange= 0 to 30 yrs
Dell et al. JBMR 27 (12):2544-2550, Dec 2012
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Other OP therapies
Denosumab (n=2:0 in FREEDOM) Odanacatib (n= 5:0 in LOFT)
Romosozumab (n=1:0 in FRAME; n=2:4 in ARCH open phase)
None reported in Abaloparatide
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Bone Characteristics
BMD (osteopenia) Shaft diameter
HRpQCT CTh CPo BV/TV
TBS
Dell et al. JBMR 27 (12):2544-2550, Dec 2012
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Morin S et al Bone Volume 83, Pages 184–189, Feb 2016;
Varus hip angle, bow leg deformity
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Pathogenetic Mechanisms
Effect of suppression of bone remodeling on:Bone’s material properties – collagen,
AGEs, increased tissue mineral density etc.
Healing of stress fractures
Relationship of hip and lower limb geometry
Genetic susceptibility – collagen abnormality, low bone turnover at baseline, etc…
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SURGICAL AND MEDICAL MANAGEMENT
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Surgical Management
Complete Fractures Fixation with IMR Reduce the gap
Incomplete Fractures Unclear when to prophylactically fix Most will not require fixation
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Case
64yo Caucasian postmenopausal woman with bilateral incomplete AFFs
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My recommendations X-rays
Yes No
CT scanto determine depth
of lucent line through the cortex and extent
around circumference
1) Reassess cause of discomfort
2) ? Stop andreassessin 6 months
Focal Cortical Reaction on plain X-ray
Bone scan
? Lucent Line
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My recommendations: DXA-Femur
Yes NoEquivocal
CT scanto determine depth
of lucent line through the cortex and extent
around circumference
1) Reassess cause of discomfort2) ? Stop and reassessin 6 months
Plain Radiographs
Focal Cortical Reaction on DXA-Femur
Bone scan(if you can’t see lucent line on X-rays)
Lucent line
Lucent line
Lucent line
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Medical Management
ASBMR Task Force RecommendationsSTOP anti-resorptive therapy (bisphosphonates and denosumab)
Then prophylactic nailing or teriparatidetherapy or both
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Medical Management
Decrease weight-bearingMuscle strengthening exercises
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Case Series of 30 pts with iAFFs• After an average of 14.8 months of TPD therapy:
However, 4 developed new lucent lines in the same femur
• healing or healed: 41%
• stable: 41%
• prophylactic surgical
intervention: 18%
stable
healing/healed
surgery
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Mrs. W -- healing
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TAFF Trial
Teriparatide for healing of incomplete Atypical Femur Fractures RCT – teriparatide vs placebo Recruiting 60 postmenopausal women Outcomes – radiographic and functional
outcomes
CALL (416)340-4843 for the TAFF trial
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GOING FORWARD…
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How do we communicate the real risk to patients? 1. Low: Complete AFFs – ~1/1000 patient years after 6-
10 years Incomplete AFFs -- ? ~1/100
2. Drug treatment according to fracture risk –benefit/risk ratio
3. Reassess drug therapies after 3-5 years, consider drug holiday for stable moderate (and ? high) risk patients
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How do we communicate the real risk to patients?If AFF: stop antiresorptive therapy decrease weight bearing activities consider bone formation therapies
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AFF Registries
Ontario AFF Cohort Quebec AFF Cohort TRAFFIC – in Australia and Singapore
In Canada, Canadian AFF Registry
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CIHR grants
Pharmacogenomics Prediction rule
We will be recruiting controls for this study
Ontario AFF Cohort – (416)340-4843
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SUMMARY
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Summary
Definition and radiographic characteristics Epidemiology Clinical Risk Factors Surgical and Medical Management Canadian AFF registry
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One Take Home Message
Patients with AFFs are
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AcknowledgmentsOthersMary BouxseinHarry GenantRoby JoehanesDoug KielSuzanne MorinElizabeth Shane
Ontario AFF CohortLianne TileAdrian LauRick AdachiRobert BleakneyRobert JosseAliya KhanSandra KimHeather McDonald-BlumerRowena RidoutLaurence RubinCarter ThorneEarl BogochAndy Wong
Canada Research Chairs
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Questions and Discussion
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OsteoConnections.com
Facebook/OsteoporosisUHN
Twitter/OsteoUHN; /UT_CESHA
Twitter/AngelaMCheung
Angela M. Cheung
Thank You